LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans

Pengpeng Li,Kang Shen,Kevin M Collins,Michael R Koelle

doi:10.7554/elife.00378

Abstract

The diverse cell types and the precise synaptic connectivity between them are the cardinal features of the nervous system. Little is known about how cell fate diversification is linked to synaptic target choices. Here we investigate how presynaptic neurons select one type of muscles, vm2, as a synaptic target and form synapses on its dendritic spine-like muscle arms. We found that the Notch-Delta pathway was required to distinguish target from non-target muscles. APX-1/Delta acts in surrounding cells including the non-target vm1 to activate LIN-12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in non-target vm1 muscle is sufficient to induce muscle arm extension from these cells. Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells. DOI:http://dx.doi.org/10.7554/eLife.00378.001.

Highlights

Functional neural circuits are generated through coordinated events during the development of the nervous system including cell type specification, neuronal process formation and synaptogenesis
UNC-40::GFP is enriched on the muscle arms, further suggesting that it might function locally to promote muscle arm growth (Figure 6C). These results indicate that the levels of UNC-40 and MADD-2 critically determine the capacity of vulval muscles to grow muscle arms and be selected as the postsynaptic target by the egg-laying motoneurons
To further explore the mechanism by which the expression of unc-40 and madd-2 was regulated by lin-12, we examined the transcriptional reporters for unc-40 and madd-2 to measure the transcriptional activity of these genes

Summary

Introduction

Functional neural circuits are generated through coordinated events during the development of the nervous system including cell type specification, neuronal process formation and synaptogenesis. An emerging literature indicates that precise synaptic connections are specified by diverse molecular mechanisms Both positive and negative regulators of synapse formation can specify local synaptic connectivity (Williams et al, 2010; Maeder and Shen, 2011). Retinal ganglion cells (RGCs) form synapses with retinal interneurons in the inner plexiform layer (IPL), generating several synaptic laminae (Sanes and Yamagata, 2009). This laminar specificity is directed by both the homophilic interactions of several immunoglobin superfamily (IgSF) proteins, including Sidekicks and Dscam, as well as the inhibitory action of semaphorins (Yamagata et al, 2002; Yamagata and Sanes, 2008; Matsuoka et al, 2011)

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Conclusion